Thomas Wolfe was one of the greatest American writers of the early 20th century. His first and most famous novel, Look Homeward Angel, brought him great fame. Wolfe published the sprawling autobiographical novel in 1929, after working on it for three years. By 1938 he was dead. His death is attributed to tuberculosis, specifically to tuberculous meningitis, that is, infection of the meninges, the brain’s lining layers of connective tissue, with the bacterial agent that causes tuberculosis, Mycobacterium tuberculosis.

In 1938, Wolfe took an extensive whirlwind tour of the American West, starting on June 20 from Portland, OR, and ending July 2 at Mt. Rainier, WA, where Wolfe caught a bus to Seattle. The trip was a huge circle that visited 11 national parks, Crater Lake in Oregon, Mt. Shasta, Yosemite, Sequoia, all in California, Grand Canyon in Arizona, Bryce and Zion in Utah, Grand Teton and Yellowstone in Wyoming, Glacier in Montana and ending at Mt Rainier in Washington. The trip was by automobile and Wolfe was joined by two newspapermen from Portland who intended to show him how great all of the highways were in the vast American West. Even before this exhausting trip, Wolfe had to get by train to Portland, which he did on the Burlington Zephyr, going through Denver, CO and Cheyenne, WY. It is true that Wolfe spent a week in Denver, so his schedule did not become extremely hectic until he reached Seattle.

On July 6, Wolfe became ill in Seattle, with a fever and cough. Wolfe was treated with cough suppressants and diathermy (electrically induced heating). Remember, this was before the advent of antibiotics. Wolfe’s cough lingered and in August he developed persistent and severe headaches. Wolfe’s Seattle physicians, perhaps sensing the end coming for him, strongly encouraged that he get quickly to the East coast, specifically to Johns Hopkins hospital in Baltimore. At Johns Hopkins, neurosurgeon Walter Dandy initially performed a trephining procedure (placement of a small hole) to relieve pressure on the brain which he thought was causing the headaches. A copious amount of fluid escaped, “spurted with terrific pressure, shooting 3 feet into the air.” Unfortunately, relief from this procedure was short lived and Dandy performed a craniotomy on Wolfe and noted tubercles on the cerebellum. Realizing the case was hopeless, Dandy immediately closed, and Wolfe died on September 15. The cause of death listed on the death certificate was tuberculous meningitis.

The family refused an autopsy, but a small amount of brain tissue had been submitted by Dandy for pathological examination in the pathology laboratory at Johns Hopkins. Although the death certificate states that the cause of death was “tuberculous meningitis,” there was no support provided for that diagnosis by the pathology report, which stated: “There are several small areas composed mostly of macrophages which suggest early tubercle formation, but this appearance is nonspecific. The brain itself appears normal. Repeated bacterial and tubercle bacilli stains are negative. Final diagnosis: Nonspecific chronic meningitis.” In other words, there is no support for the clinical diagnosis of tuberculosis rendered by Drs. Watson and Dandy.

In order to arrive at a proper clinical diagnosis in the case of Thomas Wolfe, it is necessary to understand the mentality of the 30s and the medical and popular perspective on tuberculosis. It was the AIDS of its time, striking down young fit people, many of whom were artists, like the famous eighteenth century romantic poet John Keats. Many doctors thought that tuberculosis felled Mozart. Given that Asheville, North Carolina, where Wolfe grew up in his mother’s boarding house was a haven for people diagnosed with tuberculosis, and also given that Wolfe was an artist, that he died young, that Asheville was a sanatorium town, well, it must have been tuberculosis that felled Wolfe, regardless of what the pathology report stated. But let’s read between the lines in that pathology report to see the pressure the examining pathologist was under to make a diagnosis of tuberculosis, and how he managed to resist the pressure, most likely brought to bear by the authority of Dandy and Watson. The pathologist put in a number of qualifiers and hedges to make sure that it was understood by the clinical physicians that what he was seeing was in no way confirmatory of tuberculosis. The brain tissue was normal, there were small areas composed of macrophages merely suggestive of early tubercle formation, but this finding was nonspecific. Most telling of all, repeated stains for tubercle bacilli (Mycobacterium tuberculosis) were negative. Finally, the pathologist showed great courage by signing out the case as nonspecific chronic meningitis.

Today, physicians would call these entities described by Dandy as “tubercles” by another term, namely “granuloma,” a much more generic term which in essence means the formation of small granules, or bumps if you will, in the tissue being examined. While granulomas certainly do form in tuberculosis, they are hallmarks of diseases caused by non-bacterial organisms, namely fungi. And interestingly enough, Wolfe’s Western road trip brought him straight through the epicenter of one of the most difficult to treat and widely under-recognized fungal diseases of all, caused by the organism Coccidioides immitis. This disease is coccidioidomycosis, otherwise known as San Joaquin Valley fever, or just Valley fever. Wolfe’s entire route South from Sequoia National Park to Bakersfield, CA, and then East across the Mohave desert into Arizona and up to the Grand Canyon, is the heartland of Valley fever (1). Coccidioides immitis is a full-time (endemic) resident of this vast area of the Southwest United States.

Coccidioidomycosis was first described by a medical student in Argentina in 1892. It was at first thought to be a disease similar to malaria, caused by protozoa of the Coccidia family. Similar cases were noted in California, where it was finally classified as a fungus after a couple of medical students became ill with the disease. It was thus named Coccidioides, ie, resembling Coccidia. When Thomas Wolfe became ill after his Western sojourn, clinical awareness of Coccidioidomycosis was virtually zero, whereas tuberculosis was on everyone’s mind.

What are the symptoms of Coccidioidomycosis? Fever, usually mild, chest pain, dry cough, usually not very annoying, joint pain, headache. Thomas Wolfe’s illness fits this symptom pattern very well. Meningitis caused by Coccidioides frequently results in hydrocephalus (increased intracranial pressure due to buildup of cerebrospinal fluid), which was certainly dramatic in the case of Wolfe, because cerebrospinal fluid “spurted out” when a small opening (trephining) was made to relieve the pressure. Coccidioidal meningitis is associated with headaches, fever, encephalopathy, ataxia (difficulty walking), visual disturbances, nausea and vomiting. Modern treatment includes anti-fungal agents and ventriculo-peritoneal shunts to relieve the hydrocephalus. Even today, coccidioidal meningitis is a highly morbid condition, frequently requiring multiple surgical procedures and long hospital stays (2).

The timing of the onset of Wolfe’s illness fits very well with Valley fever. He was sick within a couple of weeks of the conclusion of his trip. A recent very well documented study of an outbreak of coccidioidomycosis in Utah with defined times of exposure to soil showed onset of symptoms between 10 and 14 days after exposure (3), identical to what happened to Thomas Wolfe.

Even today, coccidioidomycosis is not usually considered as a diagnosis by physicians, even in endemic areas known to harbor the Coccidiodes organism and when travel to endemic areas is well documented by patient histories. Indeed, the incidence of the disease is increasing and appears to be spreading, leading to calls for better understanding and recognition of the disease (4) which it is clear in retrospect caused the demise of Thomas Wolfe.

Author

Ralph Giorno, MD is the Blood Whisperer. Dr. Giorno is a graduate of the University of Colorado School of Medicine and is board certified by the American Board of Pathology in Clinical Pathology, Anatomic Pathology and Immunopathology.

Dr. Giorno has worked in a large variety of settings and has been the Medical Director of hospital, independent and commercial laboratories.